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01.
arXiv (CS.LG) 2026-06-16

ExpRL: Exploratory RL for LLM Mid-Training

arXiv:2606.17024v1 Announce Type: new Abstract: Sparse reward reinforcement learning (RL) has become a standard tool for improving LLM reasoning, but its success depends critically on the coverage present in the base model. In practice, models are often primed for RL through mid-training on curated reasoning traces that teach useful primitive skills such as decomposition, verification, or self-correction. Although effective, this strategy requires manually specifying what the model should learn, and it remains unclear whether such primitive coverage is enough for much harder problems, which require combining these skills into broader solution strategies. We study a more automated approach: RL-based mid-training using large corpora of human-written question-answer data. Rather than treating reference solutions as targets to imitate, our method, ExpRL, uses them as reward scaffolds: references are hidden from the policy and used only to construct problem-specific grading rubrics for judging on-policy reasoning traces. The policy samples from the original problem prompt, while an LLM judge compares the sampled reasoning trace against the reference solution and assigns outcome-level or process-level dense rewards. This lets ExpRL reinforce partial progress, useful intermediate reductions, and productive reasoning behaviors that sparse final-answer rewards often fail to upweight. On challenging math reasoning tasks, ExpRL yields stronger RL priming than SFT, sparse-reward GRPO, and self-distillation, and provides a better initialization for subsequent sparse-reward RL. Additional mixed-domain experiments further suggest that ExpRL can extend beyond the original math-only setting.

02.
bioRxiv (Bioinfo) 2026-06-18

Structure-Based Immunoinformatics Design of a CTB-Adjuvanted Multi-Epitope Mucosal Vaccine Against Helicobacter pylori

Background: Helicobacter pylori coloniz the gastric mucosa of nearly half of the global population and is classified as a Group I carcinogen by the World Health Organization due to its strong association with gastric cancer. The growing prevalence of antibiotic-resistant H. pylori strains significantly compromises current therapeutic strategies, emphasizing the urgent need for effective prophylactic approaches. Research design and methods; In this study, a novel multi-epitope vaccine was designed targeting H. pylori, incorporating epitopes from four key virulence proteins: BabB, SabB, SabA, and VacA. Using an immunoinformatics-guided structural vaccinology approach, B- and T-cell epitopes were predicted, prioritized based on immunogenicity, conservation, population coverage, and non-homology to human proteins, and assembled into the final vaccine construct. To enhance immunogenicity and specifically stimulate mucosal immune responses, the cholera toxin B subunit (CTB) was fused at the N-terminal via an EAAAK linker, a novel application in H. pylori multi-epitope vaccines. The PADRE universal epitope and additional linkers were incorporated to optimize epitope presentation and helper T-cell activation. Results: Comprehensive evaluations of physicochemical, antigenic, allergenic, and toxic properties were conducted, followed by secondary and tertiary structure modeling, refinement, and validation. Conformational B-cell epitopes were mapped, and molecular docking, binding affinity analysis, energy minimization, and molecular dynamics simulations confirmed structural stability and receptor interactions. Codon optimization and in silico cloning predicted efficient expression in Escherichia coli, while immune simulations suggested robust humoral and cellular responses. Conclusions: This study presents a promising multi-epitope vaccine candidate against H. pylori, offering a rational framework for future experimental validation and potential clinical application.

03.
arXiv (CS.LG) 2026-06-12

A unified complexity bound for logconcave sampling

arXiv:2606.12694v1 Announce Type: cross Abstract: We give a simple, unified, and nearly tight bound for sampling arbitrary logconcave distributions from a warm start using the In-and-Out algorithm along with exponential lifting. The main new ingredient in the analysis is an improved bound on the Poincaré constant of a lifted distribution. As a consequence, the resulting convergence rate is nearly tight for both constrained settings (e.g., Gaussian restricted to a convex body) and well-conditioned settings (e.g., strongly logconcave and smooth densities).

04.
arXiv (CS.CL) 2026-06-16

HyDRA: Hybrid Dynamic Routing Architecture for Heterogeneous LLM Pools

Production LLM deployments increasingly maintain heterogeneous model pools spanning order-of-magnitude cost differences. Existing routers make binary strong-vs-weak decisions and couple learned parameters to specific model identities, requiring retraining whenever the catalog changes. We present HyDRA (Hybrid Dynamic Routing Architecture), a framework that predicts fine-grained, multi-dimensional capability requirements per query and matches them against configuration-defined model profiles via shortfall matching. A ModernBERT encoder with K=4 independent sigmoid heads scores each query along reasoning, code generation, debugging, and tool use; a shortfall-matching algorithm then selects the cheapest model whose capabilities meet the predicted requirements. The deployed predictor runs at 86 ms median CPU inference latency in production, and is fully decoupled from the model catalog – adding or removing models requires only a configuration change, with zero retraining. On SWE-Bench Verified (5-model pool: GPT-5.4-mini, Claude Haiku 4.5, GPT-5.3 Codex, Claude Sonnet 4.6, GPT-5.4), HyDRA's tunable shortfall threshold spans three regimes: peak-quality exceeds the always-strong Claude Sonnet 4.6 baseline (75.4% vs. 74.2% resolution) at 12.9% cost savings; iso-quality matches Sonnet at 54.1% cost savings, a 6x improvement over our prior in-house binary router at 9.1%; aggressive pushes savings to 72.5% for a 3.2-point quality trade. Results generalize across LiveCodeBench, BigCodeBench, and tau-bench. HyDRA is deployed to all users in GitHub Copilot's VS Code Chat auto-mode and – to our knowledge for the first time in the LLM routing literature – demonstrates language-invariant routing across CJK, European, and other script families.

05.
arXiv (CS.LG) 2026-06-12

Estimating Individualized Treatment Effects in Acute Ischemic Stroke with Causal Transformation Models (TRAM-DAG): A Multi-Centre Observational Study with External RCT Validation

arXiv:2606.12623v1 Announce Type: cross Abstract: Personalized medicine in acute ischemic stroke requires moving beyond average treatment effects (ATE) to individualized treatment effect (ITE) estimates to support treatment decisions. In acute ischemic stroke, mechanical thrombectomy has been shown to be more effective on average than lysis in randomized controlled trials (RCTs), such as the MR CLEAN study. We aim to identify which individual patients benefit most from mechanical thrombectomy compared to lysis. The outcome of interest is the modified Rankin Scale (mRS) at three months, an ordinal measure of functional disability (0: no symptoms, 6: death). We demonstrate that causal transformation models on directed acyclic graphs (TRAM-DAG) can be used for ITE estimation after being fitted on observational MAGIC multi-center stroke patient data. To ensure comparability with the MR CLEAN population, which we use for validation, we train the TRAM-DAG on a MAGIC sub-population with NIHSS at admission >= 6, corresponding to one inclusion criterion of MR CLEAN. The fitted model is then used to estimate ITEs for stroke patients in the MR CLEAN population. While these ITE estimates cannot be confirmed experimentally, we show that their average is consistent with the trial's reported ATE. Furthermore, the ITE estimates correctly rank trial patients by their observed frequency of a good outcome (mRS at three months

06.
arXiv (CS.LG) 2026-06-19

Insulin4RL: Real-Time Insulin Management in the Intensive Care Unit for Offline Reinforcement Learning

arXiv:2606.19481v1 Announce Type: new Abstract: Offline reinforcement learning (ORL) offers the potential to improve the quality of clinical decision-making using historical electronic health record (EHR) data. Current training and evaluative practices in this field rely heavily on EHR datasets that have been temporally discretised into fixed, regular time intervals. Discretisation creates fictional representations of complex clinical scenarios and compromises the generalisability of retrospective model evaluations. In this paper, we introduce Insulin4RL, a healthcare ORL dataset featuring naturally irregular inputs and actions from real clinical trajectories. Derived from MIMIC-IV, Insulin4RL comprises over 375,000 labelled decisions across 12,209 patients requiring insulin infusion titration in the Intensive Care Unit. The dataset can thus be used for research into ORL model performance under realistic clinical sampling assumptions. We provide a description of the dataset's structure and characteristics, baseline performance metrics using model-free offline reinforcement learning, and a standardised evaluation protocol using fitted Q-evaluation. We conclude with suggested areas for future research that could be addressed using this resource.

07.
arXiv (CS.AI) 2026-06-17

Cluster-Aware Dual-Level Test Specification Generation for Large-Scale Automotive Software Requirements

arXiv:2606.17197v1 Announce Type: cross Abstract: Generating test specifications that satisfy Automotive SPICE SWE.6 requirements becomes increasingly challenging and time-consuming as projects scale to thousands of requirements. Because this manual process often consumes weeks of engineering effort, automation becomes a critical necessity. However, standard Large Language Model (LLM) approaches struggle at scale: processing requirements individually discards vital inter-requirement dependencies, while feeding entire corpora at once exceeds context-window limits, leading to incomplete integration coverage and redundant test cases. This paper presents a novel "Cluster-then-Summarize" pipeline that addresses these limitations through three-stages. Requirements are embedded using sentence transformers and grouped using UMAP dimensionality reduction followed by HDBSCAN density-based clustering. This grouping utilizes an automatic minimum cluster size selection driven by a quality criterion combining normalized Silhouette and Calinski-Harabasz scores. A multi-level map-reduce summarization algorithm then distills each cluster into concise, domain-conformant descriptions while preserving quantitative thresholds and safety integrity levels. The pipeline exploits the derived cluster topology to generate test specifications at two levels: individual requirement verification and cluster-level integration tests that verify cross-requirement feature behavior. A nearby-cluster context mechanism provides bounded cross-feature awareness during each LLM call, and Retrieval-Augmented Generation grounds all outputs in ISO 26262 and ASPICE standards. Evaluation on automotive requirement datasets of varying scale demonstrates that the cluster-aware approach improves integration test coverage and maintains summarization fidelity compared to baseline methods while scaling efficiently to thousands of requirements.

08.
arXiv (CS.CV) 2026-06-16

BRDFusion: Physics Meets Generation for Urban Scene Inverse Rendering

Inverse rendering of urban scenes from captured videos enables numerous applications, including content creation and autonomous driving simulation. Physically-based rendering methods follow and control lighting physics, but suffer from reconstruction and rendering artifacts. While generative models produce realistic videos, they offer limited consistency and controllability. We present BRDFusion, a unified framework that combines two complementary models for inverse and forward rendering. Specifically, BRDFusion recovers explicit, consistent scene properties with physical modeling and alleviates optimization ambiguity with generative priors. During forward rendering, the physical model provides controllable rendering from the scene configuration, and the generative model denoises and fixes artifacts. Therefore, our method produces high-quality videos while allowing precise control, outperforming baselines in real and synthetic scenes. Moreover, BRDFusion supports novel-view relighting, night simulation, and dynamic object insertion/editing. Project page: https://shigon255.github.io/brdfusion-page/

09.
arXiv (CS.CL) 2026-06-15

MedLatentDx: Latent Multi-Agent Communication for Cross-Hospital Rare-Disease Diagnosis

Rare diseases affect over $300$ million patients across more than $7{,}000$ conditions, yet no single hospital encounters enough cases of any one condition for reliable diagnosis. Cross-hospital collaboration could help by allowing a diagnosing institution to use distributed, case-specific diagnostic evidence, but privacy regulations restrict the transmission of identifiable clinical text across institutional boundaries. This setting raises two challenges: existing medical agent systems often rely on textual evidence exchange, while raw latent states such as hidden states and KV caches may still reveal prompt-derived clinical content. We introduce MedLatentDx, a latent multi-agent communication framework in which hospital agents keep private clinical records and retrieved cases local, and send compact latent KV blocks to a host agent for rare-disease diagnosis. MedLatentDx supports two deployment settings: same-backbone hospital agents use latent KV distillation, while hospitals with different LLM backbones use cross-family latent alignment. On CrossRare-Bench, a self-built large-scale rare-disease benchmark with hospital-level partitions, MedLatentDx improves cross-hospital diagnostic performance while reducing reconstructable clinical content relative to raw-latent communication baselines.

10.
medRxiv (Medicine) 2026-06-18

MOSAIC: Methylation-Oriented Site Analysis and Information Classifier for Robust Epigenomic Classification of Acute Leukemia in Clinical Cohorts with Variable Tumor Purity

DNA methylation-based classification offers a rapid diagnostic complement to conventional molecular workflows in acute leukemia. Existing classifiers are trained on array-derived reference cohorts whose construction favors specimens with adequate tumor content, leaving clinically relevant low-purity specimens underrepresented and classifier robustness in this regime uncharacterized. On held-out low-purity specimens, existing classifiers were concordant with expert pathology in only 7 of 10 (MARLIN) and 5 of 10 (ALMA) cases, motivating a classifier built to maintain accuracy at low tumor purity. We developed MOSAIC (Methylation-Oriented Site Analysis and Information Classifier), a neural network classifier built to maintain accuracy across the full range of tumor purities encountered in clinical practice. MOSAIC is a neural network trained on publicly available array-based methylation data augmented with native methylation calls from Oxford Nanopore sequencing. MOSAIC was evaluated on low-purity specimens held out entirely from training. On these held-out low-blast leukemia specimens, all below 25% blasts and including a case at 1.4%, MOSAIC was concordant with expert pathology in every case, recovering the correct subtype where diluted disease signal would otherwise be mistaken for normal or unrelated tissue. Gradient-based saliency analysis showed that the network relies on a partially distinct set of discriminative CpG probes when classifying low-blast specimens. MOSAIC demonstrates that augmenting training with clinically representative clinical specimens yields methylation-based leukemia classification that maintains effectiveness under the variable tumor purity of real clinical cohorts.

11.
medRxiv (Medicine) 2026-06-11

Vascular Phenotyping in Parkinson's Disease: Diabetes Mellitus Operationalizes a Microvascular Metabolic Syndrome Cluster Across PPMI Diagnostic Cohorts

Background: Diabetes mellitus elevates Parkinson's disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved. Objectives: To quantify the vascular-risk burden associated with diabetes/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort. Methods: Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker). Results: Diabetes/prediabetes elevated Vascular Burden Score ({beta} = 0.53, 95% CI 0.29 to 0.77, p < 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification ({beta} = -0.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure. Conclusions: Diabetes/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.

12.
arXiv (CS.LG) 2026-06-18

Fisher Width: A Geometric Measure of Complexity on Statistical Manifolds

Authors:

arXiv:2606.18306v1 Announce Type: new Abstract: Gaussian width is a central geometric complexity measure in high-dimensional probability, compressed sensing, convex optimization, and learning theory. It quantifies the average extent of a set along random directions, thereby capturing the effective dimension of constraint sets, hypothesis classes, and descent cones. However, this notion is intrinsically Euclidean. Statistical models instead carry a natural Riemannian geometry induced by the Fisher information metric, where directions are scaled according to statistical distinguishability rather than ambient Euclidean length. We introduce Fisher width, a Fisher-geometric analogue of Gaussian width for statistical manifolds. At a parameter point $\theta$, Fisher width replaces the Euclidean identity by the local metric tensor $G(\theta)^{1/2}$, measuring the Gaussian width of the Fisher-rescaled set. This makes the resulting quantity sensitive to local statistical curvature and invariant under smooth reparameterizations. We develop the basic theory of Fisher width, showing that it retains key structural features of Gaussian width, including concentration, metric perturbation stability, and spectral comparison bounds with the Euclidean baseline, while also capturing anisotropic geometric effects invisible to Euclidean measures. As an application, we prove a generalization bound for Fisher-Lipschitz hypothesis classes and propose computable estimators, which we evaluate empirically on MNIST across three model classes. Fisher width is to statistical manifolds what Gaussian width is to Euclidean convex bodies. This work lays the foundation for studying complexity and learning on curved statistical manifolds.

13.
arXiv (CS.CL) 2026-06-11

AI Coding Agents in Social Science: Methodologically Diverse, Empirically Consistent, Interpretively Vulnerable

The deployment of LLM-based agents in scientific analysis raises opposing concerns: that agents may reduce methodological diversity, or that they may amplify the analytic flexibility through which researchers reach motivated conclusions. We argue these worries target two empirically separable layers: a design layer of methodological choices, and a verdict layer in which a decision rule maps estimates to a substantive claim. We test both by running 20 independent executions of Claude Code and Codex on a prominent immigration and social-policy against a many-analysts human baseline. At the design layer, Codex matches human methodological diversity and Claude Code produces nearly three times as many specifications; both agents' effect estimates remain broadly aligned with the human consensus, and no agent model exactly matches any human model. A prompt-induced anti-immigration researcher prior reorganizes each agent's methodological decisions but, unlike for biased human analysts in the same data, does not shift aggregate estimates or final verdicts; nor do agents reroute along the methodological axes humans use to bias their estimates. At the verdict layer, an explicit confirmatory prompt flips Claude Code's verdicts from 10% to 90% support while leaving its coefficient distribution essentially unchanged, operating through rule omission rather than rule softening. AI agents can rival or exceed human methodological diversity at the design layer while remaining vulnerable at the verdict layer. In our setting, the locus of AI bias is not estimation but interpretation.

14.
bioRxiv (Bioinfo) 2026-06-11

AGZArank: Investigating epitope-conditioned antibody binder ranking with structure-derived synthetic supervision

Computational antibody design methods can generate large libraries of candidate binders for a target epitope, but prioritizing which candidates to test experimentally remains a major bottleneck. Existing scoring approaches, including physics-based affinity estimators, structure-prediction-derived confidence measures, and inverse-folding likelihood models, provide useful proxy signals but are not explicitly optimized for early enrichment of binders among many structurally similar candidates. Here we investigate epitope-conditioned antibody binder ranking as a dedicated learning problem and introduce AGZArank, a geometric deep learning framework trained with structure-derived synthetic supervision based on normalized pseudo-energy targets. On a benchmark of 45 experimentally validated antibody-antigen interfaces, AGZArank recovered the true binder within the top ten candidates in 44.4% of cases and showed stronger generalization on post-2021 structures than ProteinMPNN, ESM-IF, and PRODIGY. Ablation experiments indicate that ranking performance depends primarily on training scale and alignment between the optimization objective and retrieval-based evaluation, rather than architectural complexity alone. These results support candidate prioritization as a distinct and tractable problem in computational antibody design.

15.
arXiv (CS.CL) 2026-06-11

Small Experiments, Cheaper Decisions: A Case Study in Staged Promotion for Micro-Pretraining

Short pretraining runs can reduce experimental cost, but they can also over-promote configurations that only look strong at tiny budgets. We study an auditable staged-promotion protocol for a fixed micro-pretraining runner on two heterogeneous host blocks: Windows A100 and Linux L40S. Starting from twelve prior-screened configurations, we use staged budgets of 2 minutes, 5 minutes, 10 minutes, 60 minutes, and 12 hours, with frozen promotion rules before expensive continuations. The early screens are intentionally treated as unstable: the 5- and 10-minute rankings are host-sensitive, and the eventual 12-hour top-ranked condition is not the mean-best condition at the replicated 10-minute gate. Because seed ranges differ across stages, these changes are operational promotion evidence, not within-seed curves. A replicated 60-minute gate keeps the Staged Factorial Screening bridge reference in the promoted set, where it ranks first in all four 60-minute host-seed cells. In the final 12-hour confirmation package, the bridge condition ranks first in all four host-seed cells across two seeds; the greedy comparator does not meet the frozen 0.010 val_bpb near-equivalence rule; and the cheaper d8/ar48 (depth-8, aspect-48) sentinel does not meet the frozen 0.020 mean-gap rule. The executed 12-hour branch spends 144 GPU-hours, and the full staged protocol records 169.2 training GPU-hours including screening stages. Continuing all four 60-minute candidates would spend 192 GPU-hours, while continuing all nine replicated 10-minute candidates would spend 432 GPU-hours. The latter numbers are accounting counterfactuals for unrun continuations, not evidence that skipped candidates could not have overtaken the reference. The result is a bounded cost-allocation finding, not a claim of global optimality, capacity-normalized superiority, or superiority over adaptive hyperparameter optimization methods.

16.
medRxiv (Medicine) 2026-06-15

Mucosal and Systemic Antibodies Associated with Clinical Protection in a Pertussis Controlled Human Infection Model

Background The engagement of mucosal and systemic immunity in preventing Bordetella pertussis colonization and infection in humans, the impact of prior vaccination on host immunity and protective outcomes, and the dynamics of the host response following exposure remain poorly understood. Methods Healthy adults were challenged with increasing colony-forming units (CFUs) doses, 106-108, of B. pertussis D420 intranasally (NCT05136599). Shedding (PCR and culturing) and symptom development were monitored up to 21 days post-challenge. Serum and nasal wash IgA and IgG were measured before challenge (baseline) and up to 6 months post-challenge. Findings Antibodies increased post-challenge only in infected individuals, primarily nasal IgA. Participants who remained uninfected had higher baseline levels of filamentous hemagglutinin (FHA)- specific mucosal IgA and IgG, and higher serum IgA against fimbriae 2/3 (FIM). FHA was negatively associated with bacterial load and was a key discriminator between shedders and non-shedders, up to one week post-challenge. By day 14 post-challenge, pertussis toxin (PT) IgG and FIM IgA in both serum and mucosal samples were negatively associated with bacterial colonization. The majority (96.7%) of acellular pertussis (aP) vaccine recipients (n=23, median age 2.0 years) became infected, compared to 69.4% of those who received whole-cell pertussis vaccine (n=36; median age 32.0 years), and their antibody responses remained distinct following infection. Interpretation Nasal FHA antibodies emerged as early predictors of protection against pertussis infection, while PT IgG and FIM IgA antibodies may reflect clearance after infection. aP-primed individuals were more susceptible to infection, despite their younger age and more recent vaccination. Funding CDC Contract #75D30122C15467 and CDC IPA Agreement #24IPA2417512 Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

17.
arXiv (CS.LG) 2026-06-11

Calibrating Decision Robustness via Inverse Conformal Risk Control

arXiv:2510.07750v3 Announce Type: replace-cross Abstract: Robust optimization safeguards decisions against uncertainty by optimizing against worst-case scenarios, yet their effectiveness hinges on a prespecified robustness level that is often chosen ad hoc, leading to either insufficient protection or overly conservative and costly solutions. Recent approaches using conformal prediction construct data-driven uncertainty sets with finite-sample coverage guarantees, but they still fix coverage targets a priori and offer little guidance for selecting robustness levels. We propose a new framework that provides distribution-free, finite-sample guarantees on both miscoverage and regret for any family of robust predict-then-optimize policies. Our method constructs valid estimators that trace out the miscoverage–regret Pareto frontier, enabling decision-makers to reliably evaluate and calibrate robustness levels according to their cost–risk preferences. The framework is simple to implement, broadly applicable across classical optimization formulations, and achieves sharper finite-sample performance. This paper offers a principled data-driven methodology for guiding robustness selection and empowers practitioners to balance robustness and conservativeness in high-stakes decision-making.

18.
arXiv (CS.CL) 2026-06-15

Hybrid Classical-Quantum Variational Autoencoder for Neural Topic Modeling

Authors:

Neural topic models enable scalable semantic discovery, but their integration with quantum hardware remains largely unexplored. We present a proof-of-concept hybrid classical-quantum variational autoencoder (VAE) for topic modeling, embedding parameterized quantum circuits within the VAE inference network while retaining a classical topic-word decoder. To address the resource constraints of quantum hardware, we propose a modified Gaussian Softmax posterior that decouples latent space dimensionality from the number of topics to be extracted, enabling the model to operate with a low-resource 10-qubit quantum device. On the AgNews dataset, the hybrid VAE outperforms state-of-the-art neural topic models (NTMs), reaching a $C_v$ coherence score of 0.71 and an NPMI score of 0.20 while preserving high topic diversity. For comparison, we also construct a fully classical variant, which also outperforms state-of-the-art models on AgNews and exhibits clear class separation in the latent space. These results demonstrate that hybrid VAEs are computationally viable even on NISQ-era devices and represent a promising direction for quantum-enhanced topic modeling.

20.
medRxiv (Medicine) 2026-06-15

GLLaucoMed: A Secure LLM-Powered Agentic Workflow for Automated Medication Extraction from Free-Text Glaucoma Clinical Notes

Purpose: To evaluate the efficacy of large language models (LLMs) in extracting medication-related information from glaucoma clinical notes in the electronic health record (EHR). Design: Cross-sectional. Subjects: 1,250 subjects in the Bascom Palmer Ophthalmic Repository. Methods: Extracted clinical notes from glaucoma-related encounters between 2014 and 2024 were labeled by two glaucoma specialists with a third serving as an adjudicator. Graders were asked to label current topical medications (CTM), proposed changes to topical medications ({Delta}TM), current oral medications (COM), and proposed changes to oral medications ({Delta}OM) in a structured fashion. The dataset was split into development (10%), validation (10%), and test (80%) sets stratified by clinician. Development and validation sets were used to engineer and refine prompts, and the held-out test set was used for model assessment. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT 5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Microsoft Azure AI Foundry within a HIPAA-compliant environment. Inter-grader agreement was assessed with Gwet AC1. LLM performance was initially assessed in a binary fashion with F1 scores, and the degree of text match among positive cases was evaluated using exact match accuracy and Jaccard Index (JI). Main Outcome Measures: F1 score, exact match accuracy, JI. Results: Gwet AC1 for intergrader agreement was 0.799, 0.888, 0.985, and 0.988 for CTM, {Delta}TM, COM, and {Delta}OM, respectively. F1 scores for CTM were 0.985, 0.971, 0.978, 0.968, and 0.970 for Claude, Deepseek, GPT, Grok, and Qwen, respectively; for {Delta}TM: 0.905, 0.826, 0.897, 0.842, 0.855, respectively; for COM: 0.923, 0.887, 0.899, 0.906, 0.894, respectively; for {Delta}OM: 0.958, 0.815, 0.937, 0.835, 0.940, respectively. Among positive cases, range of exact match accuracies for CTM (N=1354) was 0.730- 0.882 and range of JIs was 0.809-0.918. For {Delta}TM (N=404), exact match accuracy range was 0.619-0.780 and JI range was 0.668-0.827. For COM (N=47), exact match accuracy range was 0.766-0.872 and JI range was 0.765-0.870. For {Delta}OM (N=25), exact match accuracy range was 0.583-0.920 and JI range was 0.583-0.922. Conclusions: The GLLaucoMed pipeline demonstrated high performance in extracting and standardizing medication data from unstructured clinical notes, including both current medications and proposed changes. Claude and GPT exhibited the strongest performance.

21.
arXiv (CS.LG) 2026-06-18

KEPLA: A Knowledge-Enhanced Deep Learning Framework for Accurate Protein-Ligand Binding Affinity Prediction

arXiv:2506.13196v5 Announce Type: replace Abstract: Accurate prediction of protein-ligand binding affinity is critical for drug discovery. While recent deep learning approaches have demonstrated promising results, they often rely solely on structural features of proteins and ligands, overlooking their valuable biochemical knowledge associated with binding affinity. To address this limitation, we propose KEPLA, a novel deep learning framework that explicitly integrates prior knowledge from Gene Ontology and ligand properties to enhance prediction performance. KEPLA takes protein sequences and ligand molecular graphs as input and optimizes two complementary objectives: (1) aligning global representations with knowledge graph relations to capture domain-specific biochemical insights, and (2) leveraging cross attention between local representations to construct fine-grained joint embeddings for prediction. Experiments on two benchmark datasets across both in-domain and cross-domain scenarios demonstrate that KEPLA consistently outperforms state-of-the-art baselines. Furthermore, interpretability analyses based on knowledge graph relations and cross attention maps provide valuable insights into the underlying predictive mechanisms.

22.
arXiv (CS.CL) 2026-06-16

From Argument Components to Graphs: A Multi-Agent Debate with Confidence Gating for Argument Relations

Large Language Models (LLMs) are increasingly assessed and utilized in the field of Argument Mining (AM), thanks to their strong general reasoning capabilities. However, standard training-free models often miss sophisticated details, specifically in contexts where two parts of the text have to be analyzed together. Furthermore, self-correction mechanisms tend to reinforce initial hallucinations in reasoning. Overcoming these limitations typically requires expensive, domain-specific supervised fine-tuning. Recent work has shown that a multi-agent paradigm can address such weaknesses for the component classification task through dialectical refinement with a Proponent-Opponent-Judge architecture, setting a promising direction for training-free approaches in the field. In this paper, we extend and evaluate this framework on the Argument Relation Identification and Classification (ARIC) task, reformulating it as a debate over component pairs. Besides that, we introduce a confidence gating mechanism that enables debating only on the uncertain cases and accepting the initial prediction when confidence is high. On the UKP Argument Annotated Essays v2 corpus, we demonstrate that the selective debate achieves the highest Macro F1 among all training-free methods, while debate over all samples degrades performance below that of one of the baselines. All generative approaches also outperform fine-tuned RoBERTa models on Macro F1, suggesting that the under-representation of the Attack class was more damaging to supervised fine-tuning than to inference-only models. Additionally, our framework produces human-readable debate transcripts, offering interpretability absent from both single-agent and supervised classifiers.

23.
arXiv (CS.LG) 2026-06-15

The Risk Shadow of Principal Component Analysis: When 99.9999% Variance Preservation Causes Catastrophic Decision Errors

arXiv:2606.14533v1 Announce Type: new Abstract: Principal Component Analysis (PCA) preserves variance, not the information needed to detect rare catastrophic events. This paper proves the existence of a {\it Risk Shadow}: PCA can retain over 99.9999 percent of total variance while completely erasing all signal about rare, high-impact failures. When this happens, even the best possible classifier operating on the PCA representation reduces to a constant predictor. The root cause is a fundamental mismatch between variance maximization and tail risk awareness. To break the shadow, we introduce Expectile PCA (ExPCA) and Tail-Preserving PCA (TP-PCA), two methods that reweight the data covariance toward high-impact events. We prove theoretically that ExPCA strictly outperforms PCA in retaining rare-event information, and we validate our claims on synthetic data and a real-world credit card fraud detection benchmark. Our results call for a fundamental rethinking of variance-based dimensionality reduction in high-stakes decisions.

24.
arXiv (CS.AI) 2026-06-11

The Art of Interrogation: Consistency Amplifies Factuality in Spatial Reasoning

arXiv:2606.11918v1 Announce Type: new Abstract: Current Large Reasoning Models (LRMs) exhibit remarkable general capabilities but significantly underperform in spatial reasoning tasks. Existing approaches treat this gap as a knowledge deficit, relying on supervised fine-tuning (SFT) to ingest labeled spatial data from external vision sources or synthetic engines. In contrast, we argue that for many tasks, spatial reasoning capabilities are already present in pre-trained LRMs but require alignment through logical coherence under geometric 2D and 3D constraints. In this work, we propose a self-supervised reinforcement learning (RL) framework that targets the internal reasoning process without requiring ground-truth annotations. By formalizing the notion of consistency verifiers – reward functions that check for geometric and semantic consistency under transformations – we demonstrate that models can improve their spatial reasoning abilities. We use both image transformations, like flipping, and textual transformations, like swapping the order of objects in the question, and propose a new optimal transport-based RL strategy, OT-GRPO, which is a minimal-matching variant of group relative policy optimization tailored to pairwise verifiers. We show that this label-free consistency training approaches the accuracy of models trained with ground-truth supervision and achieves similar generalization across diverse tasks and data domains.

25.
arXiv (CS.LG) 2026-06-16

Greedy Coordinate Diffusion: Effective and Semantically Coherent Adversarial Attacks via Diffusion Guidance

arXiv:2606.15531v1 Announce Type: new Abstract: Fine-tuning aligned language models on benign tasks (e.g. math tutoring) systematically breaks safety guardrails, even when training data contains no harmful content. While mechanistic approaches have shed light on where alignment resides in model weights, they do not by provide a general formal framework for deriving guarantees about when fine-tuning degrades it – leaving the field without principled tools for predicting or preventing alignment collapse. We develop a local geometric framework through geometric analysis of parameter-space trajectories and apply it to understand the fragility of alignment in fine-tuning. While first-order analysis suggests orthogonal updates are safe, we prove this is illusory: the curvature of the fine-tuning loss induces second-order acceleration that can induce second-order drift into alignment-sensitive regions. We formalize a construct of our framework as the Alignment Instability Condition (AIC), three geometric properties that, when present, are sufficient to guarantee degradation. Our main result proves quartic onset of alignment degradation along gradient-flow trajectories, determined by how sharply alignment depends on specific parameters and how strongly tasks couple to these parameters. These findings yield formal sufficient conditions under which static first-order protection can fail under gradient descent. We further empirically validate the framework's foundations, showing that the Fisher Information Matrix provides a proxy for the degree of safety degradation across diverse fine-tuning.